Denali Therapeutics Announces Broad Pipeline Progress Including Positive Results From Its LRRK2 Program for Parkinson’s Disease - Seite 2

DNL201 and DNL151 (LRRK2 inhibitors) for Parkinson’s disease

Phase 1b results with DNL201 in patients with Parkinson’s disease met all biomarker goals by demonstrating greater than 50 percent inhibition of pS935 LRRK2 and pRAB10 in blood for both doses tested and improvement of the lysosomal biomarker BMP (22:6-bis-monoacylglycero-phosphate) by 20 percent and 60 percent in urine at the low and high dose, respectively.

DNL201 was generally well tolerated at the low dose and the majority of subjects experienced either no or mild adverse events (“AEs”). There was one SAE considered unrelated to drug. At the high dose, the majority of subjects experienced either mild or moderate AEs and there was one severe AE (headache) leading to dose reduction and one study withdrawal (headache and nausea). All treatment-related AEs were manageable and reversible.

Phase 1 results with DNL151 in more than 150 healthy volunteers also met all safety and biomarker goals. DNL151 was generally safe and well tolerated at all doses tested, and the majority of subjects experienced either no or mild AEs. Target and pathway engagement of greater than 50 percent and a dose-dependent reduction of BMP in urine of up to 50 percent were observed at clinically relevant doses. Given these positive data, the DNL151 Phase 1 and Phase 1b clinical trials have been expanded to study higher doses.

Denali intends to select either DNL201 or DNL151 in mid-2020 to advance into Phase 2/3 clinical trials in patients with Parkinson’s disease.

“We are excited about the results from both the DNL201 and DNL151 clinical trials which show that LRRK2 inhibition is a promising and potentially disease-modifying approach to treat Parkinson’s disease,” said Carole Ho, M.D., CMO. “We look forward to further exploring the full therapeutic potential of LRRK2 inhibitors in future clinical studies.”

DNL310 (ETV:IDS) for Hunter syndrome

Denali submitted an IND in late December 2019 for DNL310, or ETV:IDS, a recombinant form of the iduronate 2-sulfatase (“IDS”) enzyme engineered to cross the BBB using Denali’s proprietary Enzyme Transport Vehicle technology. DNL310 is intravenously administered and intended to improve overall clinical manifestations of Hunter syndrome, including both peripheral and neurological symptoms, which are not adequately addressed by currently approved therapies. If Denali receives clearance of the IND, it intends to initiate a Phase 1/2 clinical trial of DNL310 in patients with Hunter syndrome.